Transsynaptic degeneration of ventral horn motor neurons exists but plays a minor role in lower motor system dysfunction in acute ischemic rats.

BACKGROUND: As a leading cause of mortality and long-term disability, acute ischemic stroke can produce far-reaching pathophysiological consequences. Accumulating evidence has demonstrated abnormalities in the lower motor system following stroke, while the existence of Transsynaptic degeneration of contralateral spinal cord ventral horn (VH) neurons is still debated. METHODS: Using a rat model of acute ischemic stroke, we analyzed spinal cord VH neuron counts contralaterally and ipsilaterally after stroke with immunofluorescence staining. Furthermore, we estimated the overall lower motor unit abnormalities after stroke by simultaneously measuring the modified neurological severity score (mNSS), compound muscle action potential (CMAP) amplitude, repetitive nerve stimulation (RNS), spinal cord VH neuron counts, and the corresponding muscle fiber morphology. The activation status of microglia and extracellular signal-regulated kinase 1/2 (ERK 1/2) in the spinal cord VH was also assessed. RESULTS: At 7 days after stroke, the contralateral CMAP amplitudes declined to a nadir indicating lower motor function damage, and significant muscle disuse atrophy was observed on the same side; meanwhile, the VH neurons remained intact. At 14 days after focal stroke, lower motor function recovered with alleviated muscle disuse atrophy, while transsynaptic degeneration occurred on the contralateral side with elevated activation of ERK 1/2, along with the occurrence of neurogenic muscle atrophy. No apparent decrement of CMAP amplitude was observed with RNS during the whole experimental process. CONCLUSIONS: This study offered an overview of changes in the lower motor system in experimental ischemic rats. We demonstrated that transsynaptic degeneration of contralateral VH neurons occurred when lower motor function significantly recovered, which indicated the minor role of transsynaptic degeneration in lower motor dysfunction during the acute and subacute phases of focal ischemic stroke.

Colocalization of TDP-43 and stress granules at the early stage of TDP-43 aggregation in amyotrophic lateral sclerosis.

TDP-43 aggregates (skeins and round inclusions [RIs]) are frequent histopathological features of amyotrophic lateral sclerosis (ALS). We have shown that diffuse punctate cytoplasmic staining (DPCS) is the earliest pathologic manifestation of TDP-43 in ALS, corresponding to nonfibrillar TDP-43 located in the rough endoplasmic reticulum. Previous in vitro studies have suggested that TDP-43 inclusions may be derived from stress granules (SGs). Therefore, we investigated the involvement of SGs in the formation of TDP-43 inclusions. Formalin-fixed spinal cords of six ALS patients with a disease duration of less than 1 year (short duration), eight patients with a disease duration of 2-5 years (standard duration), and five normal controls were subjected to histopathological examination using antibodies against an SG marker, HuR. In normal controls, the cytoplasm of anterior horn cells was diffusely HuR-positive. In short-duration and standard-duration ALS, the number of HuR-positive anterior horn cells was significantly decreased relative to the controls. DPCS and RIs were more frequent in short-duration ALS than in standard-duration ALS. The majority of DPCS areas and a small proportion of RIs, but not skeins, were positive for HuR. Immunoelectron microscopy showed that ribosome-like granular structures in DPCS areas and RIs were labeled with anti-HuR, whereas skeins were not. These findings suggest that colocalization of TDP-43 and SGs occurs at the early stage of TDP-43 aggregation.

Early histopathological changes of secondary degeneration in the spinal cord after total MCA territory stroke.

Previous research has not demonstrated secondary degeneration of the spinal cord (SpC) motoneurons after cerebral infarct. The aim of the present study is to investigate the involvement of the anterior horn cells (AHC) in the early post-stroke period using histomorphological and immunohistochemical methods. Post-mortem analysis of the 6th cervical segment was performed in 7 patients who had total MCA stroke within 1 month before death. Nissl-stained sections were used for morphometry, while CD68 and synaptophysin (SYP) immunohistochemistry to monitor microglial activation and synaptic changes in the anterior horn (AH), respectively. Contralateral to the cerebral lesion (contralesional side), cells were smaller after 3 days and larger after 1 week of stroke, especially regarding the large alpha motoneurons. CD68 density increased mainly on the contralesional Rexed's IX lamina of the SpC. SYP coverage of the large motoneurons was reduced on the contralesional side. Early microglial activation in the AH and electrophysiological signs has suggested the possibility of impairment of anterior horn cells (AHC-s). Our study supported that early microglial activation in the contralesional side of the SpC may primarily affect the area corresponding to the location of large motoneurons, and is accompanied by a transient shrinkage followed by increase in size of the large AHC-s with a reduction of their synaptic coverage. After MCA stroke, early involvement of the SpC motoneurons may be suspected by their morphological and synaptic changes and by the pattern of microglial activation.

Long-Term Suppression of c-Jun and nNOS Preserves Ultrastructural Features of Lower Motor Neurons and Forelimb Function after Brachial Plexus Roots Avulsion.

Brachial plexus root avulsions cause debilitating upper limb paralysis. Short-term neuroprotective treatments have reported preservation of motor neurons and function in model animals while reports of long-term benefits of such treatments are scarce, especially the morphological sequelae. This morphological study investigated the long-term suppression of c-Jun- and neuronal nitric oxide synthase (nNOS) (neuroprotective treatments for one month) on the motor neuron survival, ultrastructural features of lower motor neurons, and forelimb function at six months after brachial plexus roots avulsion. Neuroprotective treatments reduced oxidative stress and preserved ventral horn motor neurons at the end of the 28-day treatment period relative to vehicle treated ones. Motor neuron sparing was associated with suppression of c-Jun, nNOS, and pro-apoptotic proteins Bim and caspases at this time point. Following 6 months of survival, neutral red staining revealed a significant loss of most of the motor neurons and ventral horn atrophy in the avulsed C6, 7, and 8 cervical segments among the vehicle-treated rats (n = 4). However, rats that received neuroprotective treatments c-Jun JNK inhibitor, SP600125 (n = 4) and a selective inhibitor of nNOS, 7-nitroindazole (n = 4), retained over half of their motor neurons in the ipsilateral avulsed side compared. Myelinated axons in the avulsed ventral horns of vehicle-treated rats were smaller but numerous compared to the intact contralateral ventral horns or neuroprotective-treated groups. In the neuroprotective treatment groups, there was the preservation of myelin thickness around large-caliber axons. Ultrastructural evaluation also confirmed the preservation of organelles including mitochondria and synapses in the two groups that received neuroprotective treatments compared with vehicle controls. Also, forelimb functional evaluation demonstrated that neuroprotective treatments improved functional abilities in the rats. In conclusion, neuroprotective treatments aimed at suppressing degenerative c-Jun and nNOS attenuated apoptosis, provided long-term preservation of motor neurons, their organelles, ventral horn size, and forelimb function.

Transplantation of viable mitochondria attenuates neurologic injury after spinal cord ischemia.

OBJECTIVES: Spinal cord ischemia (SCI) is one of the major concerns of postoperative paraplegia during major vascular or aortic surgery. Since mitochondrial dysfunction develops at the early stage of SCI, this study tested the neuronal protective effect of transplantation of viable mitochondria to the ischemic cord in rats. METHODS: SCI was induced by crossclamping of thoracic aorta at T6 level for 25 minutes, followed by release of vascular clip to restore aortic blood flow in the anesthetized rats. Mitochondria (100 µg) were isolated from freshly harvested soleus muscle and delivered via the internal jugular vein before releasing of vascular clip. The motor function was assessed independently up to 7 days after reperfusion. Spinal cords were harvested and analyzed for molecular and histological changes. RESULTS: Whole-body in vivo images acquired by an in vivo imaging system confirmed the enhancement of MitoTracker fluorescence at the regions below crossclamping and in the ischemic cord. Compared with control vehicles, transplantation of mitochondria significantly improved the lower-limb locomotor function of rats subjected to cord ischemia up to 7 days after surgery. Mitochondrial transplantation suppressed the regional endoplasmic reticulum stress in the ischemic cord by attenuating CCAAT-enhancer-binding protein homologous protein expression and restoring binding immunoglobulin protein levels. In accordance, tissue levels of interleukin-6, tumor necrosis factor-α, and caspase-3 were attenuated in the mitochondrial transplanted group. Histologic examination also showed significant increase in numbers of Nissls bodies in the neurons at the ventral horn of ischemic cord following mitochondrial transplantation. CONCLUSIONS: Our study showed that transplantation of freshly isolated mitochondria during the early stage of spinal cord ischemia-reperfusion injury suppressed the oxidative stress in endoplasmic reticulum of the injured cord, thereby reducing neuroapoptosis and improving locomotor function of rats with SCI.

Ultrastructure of spinal anterior horn cells in human Niemann-Pick type C (NPC) patient and mouse model of NPC with retroposon insertion in NPC1 genes.

Niemann-Pick disease type C (NPC) is a neurovisceral lipid-storage disease. Although NPC patients show lipid storage in anterior horn cells of the spinal cord, little information is available regarding the electron microscopic analyses of the morphologies of intra-endosomal lipid like-materials in the anterior horn cells of NPC patients. In this study, we elucidated the intra-endosomal ultrastructures in spinal anterior horn cells in an NPC patient, as well as in mutant BALB/c NPC1-/- mice with a retroposon insertion in the NPC1 gene. These morphologies were classified into four types: vesicle, multiple concentric sphere (MCS), membrane, and rose flower. The percentages of the composition in the NPC patient and NPC1-/- mice were: vesicle (55.5% and 14.9%), MCS (15.7% and 3.4%), membrane (23.6% and 57.1%), and rose flower (5.2% and 24.6%), respectively. Formation of the intra-endosomal structures could proceed as follows: (i) a vesicle or MCS buds off the endosome into the lumen; (ii) when a vesicle breaks down, a membrane is formed; and (iii) after an MCS breaks down, a rose flower structure is formed. Our new finding in this study is that ultrastructural morphology is the same between the NPC patient and NPC1-/- mice, although there are differences in the composition.

Infantile onset progressive cerebellar atrophy and anterior horn cell Degeneration-A novel phenotype associated with mutations in the PLA2G6 gene.

Pontocerebellar hypoplasia (PCH) encompasses a group of neurodegenerative disorders. There are ten known subtypes with common characteristics of pontine and cerebellar hypoplasia or atrophy, neocortical atrophy, and microcephaly. PCH is associated with anterior horn cell degeneration in PCH1a and PCH1b due to mutations in the VRK1 and EXOSC3 genes. Late onset PCH1 has been described in single case reports. The molecular etiology remains mostly unknown. We describe two siblings from a consanguineous Moslem Arabic family with a unique combination of progressive cerebellar atrophy and a SMA-like anterior horn cell degeneration due to a homozygous mutation in the PLA2G6 gene (NM_003560.2). The PLA2G6 gene encodes phospholipase A2 beta, which is involved in the remodeling of membrane phospholipids, signal transduction and calcium signaling, cell proliferation and apoptosis. Mutations in PLA2G6 are known to cause Neurodegeneration with brain iron accumulation 2 (NBIA2): Our patients have some similarities with NBIA2; both are characterized by rapidly progressive psychomotor regression and cerebellar atrophy. However, NBIA2 is not known to exhibit anterior horn cell degeneration. Our patients' phenotype is more consistent with late onset PCH1; thus, indicating that the spectrum of clinical and radiological presentations of PLA2G6 mutations should be extended and that this gene should be included in the molecular evaluation of patients with late onset PCH1.

Autophagy Is a Common Degradation Pathway for Bunina Bodies and TDP-43 Inclusions in Amyotrophic Lateral Sclerosis.

Bunina bodies (BBs) coexisting with TDP-43-immunoreactive (TDP-43-IR) skein-like inclusions (SIs) and round inclusions (RIs) in lower motor neurons are a frequent feature of sporadic amyotrophic lateral sclerosis (sALS). Since previous studies have shown that BBs and TDP-43-IR inclusions are often detected in association with autophagy-related structures (autophagosomes and autolysosomes), we examined the anterior horn cells (AHCs) of the spinal cord from 15 patients with sALS and 6 control subjects, using antibodies against autophagy-related proteins (LC3, cathepsin B, and cathepsin D). Among AHCs with SIs, 43.9% contained BBs, whereas 51.7% of AHCs with RIs did so. The cytoplasm of AHCs showed diffuse immunoreactivity for LC3, cathepsin B and cathepsin D in both sALS and controls. Ultrastructurally, SIs and mature BBs contained autophagosomes and autolysosomes. Mature BBs were localized in the vicinity of SIs. RIs also contained autophagosomes, autolysosomes, and early-stage BBs. These findings suggest that autophagy is a common degradation pathway for BBs and TDP-43-IR inclusions, which may explain their frequent coexistence.

Up-regulation of heat shock protein 27 inhibits apoptosis in lumbosacral nerve root avulsion-induced neurons.

Lumbosacral nerve root avulsion leads to widespread death of neurons in the anterior horn area of the injured spinal cord, which results in dysfunction in the lower extremities. Heat shock protein 27 (Hsp27) has been found to play cytoprotective roles under adverse conditions. However, the role of Hsp27 in neurons after lumbosacral nerve root avulsion is unknown. The aim of the present study was to investigate the effects and mechanism of action of Hsp27 on neurons after lumbosacral nerve root avulsion. It was found that Hsp27 expression was elevated in the anterior horn area of the injured spinal cord and the up-regulation of Hsp27 protected neurons against apoptosis after lumbosacral nerve root avulsion. In addition, Hsp27 plays an anti-apoptotic role by suppressing oxidative stress reactions. These findings indicated that Hsp27 may play a key role in resistance to lumbosacral nerve root avulsion-induced neuron apoptosis and may prove to be a potential strategy for improving prognosis after lumbosacral nerve root avulsion.

Disruption of the network between Onuf's nucleus and myenteric ganglia, and developing Hirschsprung-like disease following spinal subarachnoid haemorrhage: an experimental study.

Purpose/Aim of the study: Auerbach/Meissner network of lower abdominopelvic organs managed by parasympathetic nerve fibres of lumbosacral roots arising from Onuf's nucleus located in conus medullaris. Aim of this study is to evaluate if there is any relationship between Onuf's nucleus ischemia and Auerbach/Meissner network degeneration following spinal subarachnoid haemorrhage (SAH). Materials and Methods: Study was conducted on 24 male rabbits included control (Group I, n = 5), serum saline-SHAM (Group II, n = 5), and spinal SAH (Group III, n = 14) groups. Spinal SAH performed by injecting homologous blood into subarachnoid space at Th12-L4 level and followed three weeks. Live and degenerated neuron densities of Onuf's nucleus, Auerbach and Meissner ganglia (n/mm3) were determined by Stereological methods. Results: The mean degenerated neuron density of Onuf's nucleus was significantly higher in Group III than in Groups I-II (152 ± 26, 2 ± 1 and 5 ± 2/mm3 respectively, p < 0.005). The degenerated neuron density of Auerbach's ganglia was significantly higher in Group III than in Groups I-II (365 ± 112, 3 ± 1 and 9 ± 3/mm3 respectively, p < 0.005). The degenerated neuron density of Meissner's ganglia was significantly higher in Group III than in Groups I-II (413 ± 132, 2 ± 1 and 11 ± 4/mm3 respectively, p < 0.005). Conclusions: Onuf's nucleus pathologies should be considered as Auerbach/Meissner ganglia degeneration and also related Hirschsprung-like diseases in the future.

l-Theanine and NEP1-40 promote nerve regeneration and functional recovery after brachial plexus root avulsion.

Brachial plexus root avulsion causes severe sequelae Treatments and prognosis face many problems, including inflammatory reaction, oxidative damage, and myelin related inhibitory effect. l-Theanine has anti-inflammatory, anti-oxidative, and neuroprotective effects. NEP1-40 competitively inhibits Nogo-66 receptor (NgR1) promotes axonal regeneration. Forty-eight Sprague-Dawley rats were randomly assigned into four groups to establish an animal model of brachial plexus root avulsion. Inflammation and oxidative damage were evaluated by spectrophotometry and motor function of the upper limbs was assessed via Terzis grooming test after modeling. Immunofluorescence and hematoxylin and eosin staining were utilized to determine the content of reactive oxygen species, activation of microglial cells, neuroprotection, and nerve regeneration. Compared with the control group, the L-Theanine + NEP1-40 group had significantly decreased myeloperoxidase, malondialdehyde, interleukin-6, reactive oxygen species, and microglial cells, significantly increased score on the Terzis grooming test, increased motor neuron content, and thickened muscle fibers, increased area, and appearance of large and clear motor endplate structures. The results of this study suggest that l-Theanine combined with NEP1-40significantly promoted nerve regeneration after brachial plexus root avulsion, and may be a potential treatment for promoting nerve regeneration. Possible mechanisms underlying these results are alleviation of oxidative damage and inflammatory responses in the injured area and antagonism of myelin inhibition.

Colocalization of Bunina bodies and TDP-43 inclusions in a case of sporadic amyotrophic lateral sclerosis with Lewy body-like hyaline inclusions.

Sporadic amyotrophic lateral sclerosis (sALS) is characterized pathologically by loss of upper and lower motor neurons with occurrence of transactivation response DNA-binding protein 43 kDa (TDP-43)-immunoreactive skein-like and round hyaline inclusions. Lewy body-like hyaline inclusions (LBHIs) are also found in a small proportion of sALS cases as well as in individuals with familial ALS with mutations in the Cu/Zu superoxide dismutase (SOD1) gene. LBHIs in sALS are immunopositive for TDP-43, but not for SOD1. The occurrence of Bunina bodies (BBs) is another key pathological feature of sALS. BBs are immunonegative for TDP-43 but immunopositive for cystatin C, transferrin, peripherin and sortilin-related receptor CNS expressed 2 (SorCS2). Despite differences between BBs and TDP-43 inclusions in terms of protein constituents and ultrastructure, the two inclusions are known to be linked. We recently encountered a case of sALS of 10 months duration in which many round hyaline inclusions, LBHIs and BBs were found in the anterior horn cells of the spinal cord. Our immunohistochemical and ultrastructural examinations revealed the presence of BBs within the skein-like and round hyaline inclusions, and in the LBHIs. Colocalization of BB-related proteins (cystatin C, transferrin and SorCS2) and TDP-43 was also confirmed in the halo of LBHIs as well as in the marginal portion of the skein-like and round hyaline inclusions. These findings suggest that there is some relationship between BBs and TDP-43-immunoreactive inclusions in terms of their formation processes.

Systemic overexpression of SQSTM1/p62 accelerates disease onset in a SOD1H46R-expressing ALS mouse model.

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by a selective loss of upper and lower motor neurons. Recent studies have shown that mutations in SQSTM1 are linked to ALS. SQSTM1 encodes SQSTM1/p62 that regulates not only autophagy via the association with MAP1LC3/LC3 and ubiquitinated proteins but also the KEAP1-NFE2L2/Nrf2 anti-oxidative stress pathway by interacting with KEAP1. Previously, we have demonstrated that loss of SQSTM1 exacerbates disease phenotypes in a SOD1H46R-expressing ALS mouse model. To clarify the effects of SQSTM1 overexpression in this model, we generated SQSTM1 and SOD1 H46R double-transgenic (SQSTM1;SOD1 H46R ) mice. SQSTM1;SOD1 H46R mice exhibited earlier disease onset and shorter lifespan than did SOD1 H46R mice. Conversely, disease progression after the onset rather slightly but significantly slowed in SQSTM1;SOD1 H46R mice. However, there were observable differences neither in the number of Nissl positive neurons nor in the distribution of ubiquitin-positive and/or SQSTM1-positive aggregates between SOD1 H46R and SQSTM1;SOD1 H46R mice. It was noted that these protein aggregates were mainly observed in neuropil, and partly localized to astrocytes and/or microglia, but not to MAP2-positive neuronal cell bodies and dendrites at the end-stage of disease. Nonetheless, the biochemically-detectable insoluble SQSTM1 and poly-ubiquitinated proteins were significantly and progressively increased in the spinal cord of SQSTM1;SOD1 H46R mice compared to SOD1 H46R mice. These results suggest that overexpression of SQSTM1 in SOD1 H46R mice accelerates disease onset by compromising the protein degradation pathways.

Functional Divergence of Delta and Mu Opioid Receptor Organization in CNS Pain Circuits.

Cellular interactions between delta and mu opioid receptors (DORs and MORs), including heteromerization, are thought to regulate opioid analgesia. However, the identity of the nociceptive neurons in which such interactions could occur in vivo remains elusive. Here we show that DOR-MOR co-expression is limited to small populations of excitatory interneurons and projection neurons in the spinal cord dorsal horn and unexpectedly predominates in ventral horn motor circuits. Similarly, DOR-MOR co-expression is rare in parabrachial, amygdalar, and cortical brain regions processing nociceptive information. We further demonstrate that in the discrete DOR-MOR co-expressing nociceptive neurons, the two receptors internalize and function independently. Finally, conditional knockout experiments revealed that DORs selectively regulate mechanical pain by controlling the excitability of somatostatin-positive dorsal horn interneurons. Collectively, our results illuminate the functional organization of DORs and MORs in CNS pain circuits and reappraise the importance of DOR-MOR cellular interactions for developing novel opioid analgesics.

Atypical lower motor neuron disease with enlargement of Nissl substance: Report of an autopsy case.

The patient was an 81-year-old woman diagnosed with atypical motor neuron disease who died after a long clinical course (7.5 years without mechanical assistance of ventilation) characterized by lower motor neuron signs and symptoms. Upper motor neuron signs and cognitive impairment were not apparent. Autopsy demonstrated severe neuronal loss in the anterior horn of the spinal cord, and some of the remaining neurons showed enlargement of Nissl substance and apparent thickening of the nuclear envelopes. No Bunina bodies, skein-like inclusions, or structures immunoreactive for phosphorylated transactivation response DNA-binding protein 43 were found. Immunoreactivity for superoxide dismutase-1 was focally seen in the enlarged Nissl substance. Ultrastructural examination demonstrated an increase of rough-surfaced endoplasmic reticulum (rough ER) and free ribosomes, disaggregation of polyribosomes, and dispersion of free ribosomes. Cisterns of rough ER were slightly dilated, and some of them were closely attached to the nuclear envelopes. Enlargement of Nissl substance may be related to "ER stress", and the abnormal findings of rough ER and free ribosomes may represent a degenerative process. However, another possibility, that they represent a compensatory hyperplastic change, cannot be excluded. The close attachment of cisterns of rough ER to the nuclear envelopes may be a mechanism to support or compensate for the abnormally-fragile nuclear envelopes.
.

Pathological and immunoblot analysis of phosphorylated TDP-43 in sporadic amyotrophic lateral sclerosis with pallido-nigro-luysian degeneration.

Transactivation response DNA-binding protein 43 kDa (TDP-43) is a key protein of sporadic amyotrophic lateral sclerosis (ALS), and phosphorylated form of TDP-43 (p-TDP-43) is a major pathological protein that accumulates in sporadic ALS. p-TDP-43 is found not only in primary motor neurons, but often propagates to non-motor systems as well. However, pallido-nigro-luysian (PNL) degeneration (PNLD) is rarely associated with ALS. We describe here a 68-year-old ALS patient presenting severe PNLD. He had difficulty walking due to poor movement of his right leg, and was diagnosed as having Parkinson's disease because of akinesia. About 2 years after onset, weakness of his left hand and leg led to a diagnosis of ALS. Tube feeding and non-invasive positive-pressure ventilation were initiated. He died of respiratory failure at the age of 71. There was no family history of either neurological disorders or dementia. Neuropathological examination revealed severe loss of neurons and gliosis in the PNL system in addition to the upper and lower motor neuron system. p-TDP-43 pathology was widespread in the PNL and motor neuron systems and also in the amygdala and hippocampus where no significant gliosis or neuronal loss was detected. Synuclein pathology was not observed in the investigated areas. Immunoblot analysis of p-TDP-43 C-terminal fragments showed a type B band pattern consistent with sporadic ALS. This is the first case of ALS with PNLD, in which p-TDP-43 distribution was widespread in the hippocampal formation (Nishihira type 2 and Brettschneider stage 4), and the type B immunoblot pattern was confirmed. Our case indicated that the PNL system can be involved in the disease process in sporadic ALS cases, although rarely. We also reviewed previous autopsy cases of ALS with PNLD to clarify the clinicopathological features.

Monoamine oxidase-B inhibitor protects degenerating spinal neurons, enhances nerve regeneration and functional recovery in sciatic nerve crush injury model.

Monoamine oxidase-B (MAOB), a flavin adenine dinucleotide (FAD), is an enzyme which catalyzes the oxidation of amines. MAOB is proposed to play a major role in the pathogenesis of neurodegeneration through the production of reactive oxygen species (ROS) and neurotoxins. The present study was designed to outline the effects of the MAOB inhibitor (MAOB-I) on neuroprotection of spinal neurons, regeneration of sciatic nerve fibers, and recovery of sensory-motor functions in the sciatic nerve crush injury model. Male Wistar rats (4-months-old) were assigned to i) Naïve (N), ii) Sham (S), iii) Sciatic nerve crush and treated with saline (CRUSH + SALINE) and iv) Sciatic nerve crush and treated with MAOB inhibitor (CRUSH + MAOB-I) groups (n = 10/group). In groups iii and iv, the crush injury was produced by crushing the sciatic nerve followed by treatment with saline or MAOB-I (Selegiline® 2.5 mg/kg) intraperitoneally for 10 days. Behavioral tests were conducted from week 1 to week 6. At the end of the study, sciatic nerve and lumbar spinal cord were examined by immunohistochemistry, light and electron microscopy. MAOB-I treatment showed significant improvement in sensory and motor functions compared to saline treatment (p < 0.05-0.001) in injured nerves. The morphological study showed a significantly increased number of nerve fibers in sciatic nerve distal to the site of injury (p < 0.05), with better myelination pattern in CRUSH + MAOB-I treated group compared to CRUSH + SALINE group. Spinal cord ventral horns showed a significant increase in the number of NeuN-immunoreactive neurons in the MAOB-I treated group compared to Saline treated group (p < 0.01). MAOB-I has a significant potential for protecting the degenerating spinal cord neurons and enhancing the regeneration of injured sciatic nerve fibers following crush injury.